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Liquid Biopsy-Based Colorectal Cancer Screening Lacks Cost-Effectiveness, Economic Analysis Finds

NEW YORK – New research in the journal JAMA Network Open suggests conventional colonoscopy remains the most cost-effective approach to universal colorectal cancer (CRC) screening in average-risk adult individuals in the US, over circulating tumor DNA-based methods.

"Our analysis results showed that colonoscopy remains the most cost-effective screening tool for colorectal cancer," first author Zainab Aziz, a medical student working in senior author Chin Hur's Columbia University Irving Medical Center lab, explained in an email, noting that liquid biopsy-based tests "must reduce in price and become better at detecting early-stage cancers and pre-cancerous lesions in order to be a viable screening option."

Although the US Preventive Services Task Force recommends CRC screening starting at 45 years of age in individuals deemed at average risk of the condition, the team noted that universal CRC screening rates remain relatively low in the US, at roughly 60 percent.

Given the growing interest in blood-based screens for CRC, the investigators set out to assess the cost-effectiveness of that strategy in the first- or second-line screening setting, building on prior studies that compared the cost-effectiveness of conventional screening methods, such as colonoscopy with stool-based DNA testing. There are no blood tests recommended currently for CRC screening, the researchers noted.

"Ours is the first study to directly compare the cost-effectiveness of novel liquid biopsy to current screening tools, such as stool tests and colonoscopy," Aziz said.

Using a simulated cohort that included 45-year-old individuals with an average CRC risk, the team performed a Markov model-based economic analysis that compared the estimated life expectancy, total cost, and cost of life-years gained — known as the incremental cost-effectiveness ratio — of no screening and five different screening methods: colonoscopy, testing on DNA in stool (S-DNA), fecal immunochemical testing (FIT), liquid biopsy, or liquid biopsy after colonoscopy refusal.

The analyses assumed 100 percent adherence to the liquid biopsy-based screening approaches, and 60.6 percent adherence to the remaining testing methods, the investigators explained, noting that cost-effectiveness was based on a "US willingness-to-pay threshold" defined as $100,000 for each year of life gained.

Findings from the simulation study lined up with those from past studies when it came to confirming the cost-effectiveness of colonoscopy-based screening, Aziz explained, supporting the notion that the latest results provide an accurate picture of the economic impact of other screening strategies considered.

"Previous studies have compared the cost-effectiveness of colonoscopy and stool-based tests, and from that perspective, our results are the same," she said. "Having other studies to compare our work to allowed us to validate our modeling results."

As reported in the past, the team saw the greatest cost-effectiveness for colonoscopy, which had an estimated incremental cost-effectiveness ratio of just over $28,000 per life-year gained in the simulation analysis. The life-year gain for colonoscopy appeared to exceed those of the less expensive FIT approach and the more expensive S-DNA approach.

In contrast, the combined colonoscopy-liquid biopsy method, which relied on circulating tumor DNA testing in individuals who balked at colonoscopy-based CRC screening, appeared to have the most pronounced life-year gain, the researchers reported, but had a much higher incremental cost-effectiveness ratio of more than $377,500 per life year.

"In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population," the authors reported, "and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance."

Nevertheless, the authors noted that liquid biopsy-based CRC screening could become less expensive. "In the future as technology improves, it is possible that these tests will become cost-effective options," Aziz said.

In a corresponding commentary, University of Utah internal medicine researcher John Inadomi, who was not involved in the study, noted that the new work "examines an important step in the dissemination of new technologies to improve cancer screening and possibly reduce racial and ethnic disparities in CRC outcomes."

Given the cost-effectiveness results reported in the study, Inadomi cautioned that "in our attempts to increase access to screening, we may inadvertently increase the barrier to screening in certain populations, especially individuals for whom the cost of screening is greater with blood-based tests due to the retail price (for those without insurance) or copayments (for those with high-deductible insurance)."